In several ocular diseases important ocular surface pathology results from a deficiency in the secretion of lacrimal gland fluid. The long-term objective of this application is to improve treatment of aqueous tear deficiency through topical pharmacologic, and/or biomechanical means. Bromhexine may stimulate or alter the character or lacrimal gland secretion, and this project will determine the effect of bromhexine on lacrimal gland secretion in the rabbit model. Bromhexine will be administered to the lacrimal gland via the lingual artery. Lacrimal fluid flow rate, osmolarity, and protein concentration will be monitored by collecting fluid directly from the cannulated lacrimal gland excretory duct. If bromhexine is found to change any parameter of lacrimal gland fluid secretion, the mechanism of action will be studied. The effect of orally administered bromhexine will be studied over the course of several hours as well as after administration for several weeks, again by cannulating the excretory duct in anesthetized rabbits. There is good reason to expect that the ocular surface epithelium, like the corneal endothelium, has specific electrolyte and metabolite needs. These requirements would be satisfied in part by lacrimal gland fluid, but may not be satisfied by currently available medications. To optimize topical therapy, these requirements need to be defined. This project will determine the essential fluid, electrolyte, and metabolite requirements of the ocular surface epithelium normally satisfied by lacrimal gland fluid. Toxicity of potential "artificial lacrimal fluid" solutions will be tested by short-term ocular bathing and chronic infusion into the intact tear film with an implantable infusion pump system. Then the long-term capability of the developed solutions to maintain epithelial health while they are infused into the tear film in the absence of lacrimal gland secretion will be investigated. Toxicity and epithelial health will be evaluated by determining corneal epithelial glycogen levels and by epithelial morphological studies.